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IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial. OBJECTIVE: To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations. DATA SOURCES: MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. STUDY SELECTION: Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non−GLP-1 RA drugs in adults. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021. RESULTS: A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P  = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P  = .03 for interaction). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021271599

Premature ovarian insufficiency (POI) affects seriously physical and mental health of the patients. Studies show that acupuncture may be promising in treating POI, yet evidence is insufficient. International patient registry, one form of observational study, is designed for evaluating effectiveness and safety of acupuncture in real-world clinical settings. We will face a series of opportunities and challenges. The opportunities are as follows: (1) Interdisciplinary cooperation can improve the effect of acupuncture for POI. (2) The protocol for acupuncture to treat POI has room for improvement. (3) The patient registry study can make up the shortcomings of randomized controlled trials. (4) The patient registry study can collect real-world data and explore responses of different populations to acupuncture and can be the foundation for the successive studies. International patient registry may face technological, ethical and financial challenges, while the established International Patient Registry Platform of Acupuncture-Moxibustion (www.amreg.org:8082/v3) is actively responding to these challenges. Till now there have been more than 300 patients of POI enrolled on this platform.

To help researchers selecting appropriate data mining models to provide better evidence for the clinical practice of Traditional Chinese Medicine (TCM) diagnosis and therapy.

To assess the efficacy and safety of Reduning injection for fever, rash, and ulcers in children with mild hand, foot, and mouth disease (HFMD).

ObjectiveTo examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases.DesignSystematic review and pairwise and network meta-analysis.Data sourcesPubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021.Eligibility criteriaRandomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs.Main outcome measuresComposite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases.Data extraction and data synthesisTwo reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals.ResultsA total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists.ConclusionsDipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice.Systematic review registrationPROSPERO CRD42021271647.

Summary Introduction:Fenofibrate, an agonist of peroxisome proliferator‐activated receptor‐α (PPAR‐α), has a vascular protective effect. Aims:We investigated the effect of the PPAR‐α agonist on coronary artery endothelial function in patients with hypertriglyceridemia. Methods:Fifty‐eight patients with hypertriglyceridemia were divided into two groups: control (no treatment; n = 23) and fenofibrate treatment (n = 35), 200 mg/d, for 6 months. The patients had undergone rest and adenosine treatment to induce hyperemia for quantification of coronary flow velocity reserve (CFVR) by noninvasive Doppler echocardiography before treatment and at 6‐month follow‐up. Pulse wave velocity (PWV) was measured before treatment and at 6‐month follow‐up. Results:CFVR was significantly improved with fenofibrate treatment as compared with baseline level and control group (3.14 ± 0.36 vs. 2.80 ± 0.58 and 2.79 ± 0.65, P< 0.01 and 0.05, respectively), with no difference between baseline levels and untreated controls. In addition, at 6 months, plasma level of homocysteine was significantly increased with fenofibrate treatment as compared with at baseline and control group (median 18.13 [range 14.46–22.02]μmol/L vs. 14.09 [12.01–18.81] and 13.34 [9.69–17.06]μmol/L, P< 0.001 and 0.01, respectively). Furthermore, at 6 months, PWV was significantly decreased with fenofibrate treatment as compared with control group (1446 ± 136 cm/s vs. 1570 ± 203 cm/s, P< 0.05). Conclusions:Treatment with PPAR‐α agonist fenofibrate significantly improved CFVR and arterial stiffness in patients with hypertriglyceridemia. This endothelial protective effect may be reduced in part by the side effect of increasing homocysteine.